Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance.

Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the "weep" response that is critical for type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here, we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.

Tuft cell-derived acetylcholine regulates epithelial fluid secretion.

Tuft cells are solitary chemosensory epithelial cells that can sense lumenal stimuli at mucosal barriers and secrete effector molecules to regulate the physiology and immune state of their surrounding tissue. In the small intestine, tuft cells detect parasitic worms (helminths) and microbe-derived succinate, and signal to immune cells to trigger a Type 2 immune response that leads to extensive epithelial remodeling spanning several days. Acetylcholine (ACh) from airway tuft cells has been shown to stimulate acute changes in breathing and mucocilliary clearance, but its function in the intestine is unknown. Here we show that tuft cell chemosensing in the intestine leads to release of ACh, but that this does not contribute to immune cell activation or associated tissue remodeling. Instead, tuft cell-derived ACh triggers immediate fluid secretion from neighboring epithelial cells into the intestinal lumen. This tuft cell-regulated fluid secretion is amplified during Type 2 inflammation, and helminth clearance is delayed in mice lacking tuft cell ACh. The coupling of the chemosensory function of tuft cells with fluid secretion creates an epithelium-intrinsic response unit that effects a physiological change within seconds of activation. This response mechanism is shared by tuft cells across tissues, and serves to regulate the epithelial secretion that is both a hallmark of Type 2 immunity and an essential component of homeostatic maintenance at mucosal barriers.

Feasibility of real-time workflow segmentation for tracked needle interventions.

Computer-assisted training systems promote both training efficacy and patient health. An important component for providing automatic feedback in computer-assisted training systems is workflow segmentation: the determination of what task in the workflow is being performed. Our objective was to develop a workflow segmentation algorithm for needle interventions using needle tracking data. Needle tracking data were collected from ultrasound-guided epidural injections and lumbar punctures, performed by medical personnel. The workflow segmentation algorithm was tested in a simulated real-time scenario: the algorithm was only allowed access to data recorded at, or prior to, the time being segmented. Segmentation output was compared to the ground-truth segmentations produced by independent blinded observers. Overall, the algorithm was 93% accurate. It automatically segmented the ultrasound-guided epidural procedures with 81% accuracy and the lumbar punctures with 82% accuracy. Given that the manual segmentation consistency was only 84%, the algorithm's accuracy was 93%. Using Cohen's d statistic, a medium effect size (0.5) was calculated. Because the algorithm segments needle-based procedures with such high accuracy, expert observers can be augmented by this algorithm without a large decrease in ability to follow trainees in a workflow. The proposed algorithm is feasible for use in a computer-assisted needle placement training system.

Perk Tutor: an open-source training platform for ultrasound-guided needle insertions.

Image-guided needle placement, including ultrasound (US)-guided techniques, have become commonplace in modern medical diagnosis and therapy. To ensure that the next generations of physicians are competent using this technology, efficient and effective educational programs need to be developed. This paper presents the Perk Tutor: a configurable, open-source training platform for US-guided needle insertions. The Perk Tutor was successfully tested in three different configurations to demonstrate its adaptability to different procedures and learning objectives. 1) The Targeting Tutor, designed to develop US-guided needle targeting skills, 2) the Lumbar Tutor, designed for practicing US-guided lumbar spinal procedures, and (3) the Prostate Biopsy Tutor, configured for US-guided prostate biopsies. The Perk Tutor provides the trainee with quantitative feedback on progress toward the specific learning objectives of each configuration. Configurations were implemented through simple rearrangement of hardware and software components, attesting to the modularity and ease of configuration. The Perk Tutor is provided as a free resource to enable research and development of educational programs for US-guided intervention.